2008 nobel Laureates
The Nobel Prize in Chemistry 2008
Osamu Shimomura
 University of california, san diego
J. Henriksson/SCANPIX
tom kleindinst/marine biological laboratory
“for the discovery and development
of the green fluorescent protein, GFP”
Martin Chalfie
Roger Y. Tsien
1/3 of the prize
1/3 of the prize
1/3 of the prize
Born: 1928
Born: 1947
Born: 1952
Birthplace: Japan
Birthplace: United States
Birthplace: United States
Nationality:
Japanese citizen
Nationality:
US citizen
Nationality:
US citizen
Current position:
Professor Emeritus, Marine
Biological Laboratory (MBL),
Woods Hole, Massachusetts,
USA, and Boston
University Medical School,
Massachusetts, USA
Current position:
William R. Kenan Jr
Professor of Biological
Sciences, Columbia
University, New York,
New York, USA
Current position: Professor, University of
California, San Diego,
La Jolla, California, USA
chemistry 7
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2008 nobel Laureates
Phantatomix/Science Photo Library
Speed read: Illuminating biology
T
he discoveries awarded the one-hundredth
Nobel Prize in Chemistry are a shining example
of how fundamental research in one area of
science can sometimes lead to highly beneficial
applications in another. In this case, finding the key to
how a marine organism produces light unexpectedly
ended-up providing researchers with a powerful array
of tools with which to visualise cell biology in action.
Osamu Shimomura purifies a blue
luminescent protein from the jellyfish
Aequorea victoria that he names
aequorin; he also isolates a protein
displaying bright green fluorescence
that is later named green fluorescent
protein (GFP)
1962
The story begins with Osamu Shimomura’s research
into the phenomenon of bioluminescence, in which
chemical reactions within living organisms give off
light. While studying a glowing jellyfish in the early
1960s he isolated a bioluminescent protein that
gave off blue light. But the jellyfish glowed green.
Further studies revealed that the protein’s blue light
was absorbed by a second jellyfish protein, later
called green fluorescent protein (GFP), which in turn
re-emitted green light. The ability of GFP to process
blue light to green (its fluorescence) was found to be
integral to its structure, occurring without the need
for any accompanying factors.
In 1988, Martin Chalfie heard about GFP for the first
time, and realised that its ability for independent
fluorescence could perhaps make it an ideal cellular
beacon for the model organisms he studied. Using
molecular biological techniques, Chalfie succeeded
in introducing the gene for GFP into the DNA of the
small, almost transparent worm Caenorhabditis
elegans. GFP was produced by the cells, giving off
Martin Chalfie hears
about GFP for the first
time, and realises it could
be used to map proteins
in the transparent
nematode worm,
Caenorhabditis elegans
1979
Shimomura shows that
GFP contains a special
chromophore, a
chemical group that
absorbs and emits light
1988
1992
Chalfie obtains the GFP gene from
Douglas Prasher, and Chalfie’s PhD
student Ghia Euskirchen expresses
it in Escherichia coli – the bacteria
glow green in UV light without the
addition of any other factors
Timeline: Milestones for the 2008 Nobel Laureates in Chemistry, Osamu Shimomura, Martin Chalfie &
Roger Y. Tsien.
8 chemistry
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2008 nobel Laureates
Tsien lab, university of California, San Diego
its green glow without the need for the addition of
any extra components, and without any indication
of causing damage to the worms. Subsequent work
showed that it was possible to fuse the gene for GFP
to genes for other proteins, opening-up a world of
possibilities for tracking the localisation of specific
proteins in living organisms.
The opportunities offered by GFP were immediately
obvious to many, as was the desirability of extending
the range of available tags. Roger Tsien first studied
precisely how GFP’s structure produces the observed
green fluorescence, and then used this knowledge to
tweak the structure to produce molecules that emit
light at slightly different wavelengths, which gave
tags of different colours. In time, his group added
further fluorescent molecules from other natural
sources to the tag collection, which continues to
expand. Complex biological networks can now be
labelled in an array of different colours, allowing
visualisation of a multitude of processes previously
hidden from view.
Chalfie expresses GFP
in C. elegans and shows
it can be used to track
the location of specific
proteins
1994
Roger Tsien shows how the
GFP chromophore is formed
in a chemical reaction that
requires oxygen, without the
help of other proteins
Mikhail Matz and Sergei
Lukyanov discover six
GFP-like proteins in
fluorescent corals, including a
red protein called DsRED
1994–1998
Tsien and collaborators tweak
the structure of GFP to
produce new variants that
shine more strongly and
produce different colours,
such as cyan, blue and yellow
1999
2000–2002
Tsien produces stable variants
of DsRED that glow in shades
of red, orange and pink –
complex biological networks
can now be labelled using all
the colours of the rainbow
chemistry 9
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2008 nobel Laureates
In his own words: Osamu Shimomura
Tom Kleindist/Marine
Biological Laboratory
“To get success, everybody has to overcome any
difficulty on the way.” Osamu Shimomura
can speak from experience. As a teenager living
12 kilometres away from Nagasaki, he felt the blast
of the atomic bomb explosion in August 1945.
“I was soaked by black rain. So, I was contaminated
by the radioactivity, a lot of strong radioactivity.
But fortunately still I’m alive.”
“I don’t do my research for
application or any benefit. I just
do my research to understand
why jellyfish luminesce”
Osamu Shimomura holding some of the
hundreds of thousands of jellyfish specimens
that he collected from Friday Harbor.
The thousands of scientists worldwide who have
benefited from the fruits of Shimomura’s labours
will no doubt share his sentiment. Thanks to his
discovery of green fluorescent protein (GFP) in
jellyfish they have one of the most important tools at
their disposal for visualizing life at the microscopic
level; although Shimomura is quick to point out that
there was only ever a single purpose behind his
studies. “I don’t do my research for application or
any benefit. I just do my research to understand why
jellyfish luminesce, and why that protein fluoresces.”
jellyfish did he need to collect? “Our schedule was
50,000 per summer, in one or two months.” These
remarkable expeditions took place every summer for
19 years, collecting a staggering 850,000 jellyfish in
total. “That’s classical biochemistry, not genetics or
something like that,” says Shimomura.
Osamu Shimomura
Discovering GFP in jellyfish took considerable effort.
“What we needed to do to study that protein is we
have to get large amounts of that protein. So, we
collected huge numbers of jellyfish by going to Friday
Harbor, Washington, every summer.” Just how many
When Osamu Shimomura started studying
glowing jellyfish, he had no idea that it would
lead to a scientific revolution.
Shimomura says that GFP is one of many, still
undiscovered, molecules in nature that emit light,
but he fears that the demands of carrying out such
labour intensive and uncertain research will deter
young scientists from looking for them. “They prefer
easier research. And they prefer research subjects
that you can see the results; that you are sure to
get the results.” So, what advice would Shimomura
give to young people who are interested in entering
science? “Study whatever they are interested in,
and don’t give up on the way until they finish the
subject. Good subjects have a lot of difficulty. If one
gives up, on the way; that’s it, that’s finished.”
By way of illustrating his philosophy on never
finishing until the job is done, Shimomura continues
to work in a laboratory set up in the basement of his
house, despite officially retiring in 2001. Recently
he has been working on writing papers, and also
helping other people, but he resigns himself to the
inevitable change that will result from being awarded
the Nobel Prize. “I think it’s hopeless to work out of
the laboratory for the next several months, I guess.”
This article is based on a telephone interview with Osamu Shimomura following the announcement of the 2008 Nobel Prize in
Chemistry. To listen to the interview in full, visit http://nobelprize.org/nobel_prizes/chemistry/laureates/2008/shimomura-interview.html
10 chemistry
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2008 nobel Laureates
In his own words: Martin Chalfie
Looking back at the moment 20 years ago when he
first heard about green fluorescent protein (GFP)
in a seminar, Chalfie recalls his instant realisation
that GFP could be used as a cellular beacon in
his studies in the nematode worm, known as
Caenorhabditis elegans. “One of the great things
about working on C. elegans was the fact that it
was transparent, and so when I first heard that
seminar describing GFP, and realised, ‘I work on
this transparent animal, this is going to be terrific!
I’ll be able to see the cells within the living animal’.”
The story from initial
thought to seeing cells
glow in C. elegans involved
an extraordinary chain of
events over the following
two years. Chalfie contacted
a researcher called Douglas
Prasher who was studying
GFP, and they agreed that once Prasher had cloned
the gene that encodes GFP they would see if they
could make it glow in C. elegans. But while Prasher
finished cloning the GFP gene, Chalfie had taken a
sabbatical, moving from Columbia University to the
University of Utah to work with his then new wife.
“When he finished the cloning, he got in touch with
me, or he tried to,” recalls Chalfie. Prasher tried to
contact Chalfie at Columbia University, and then at
the University of Utah, “…but someone must have
The Caldwell Laboratory,
University of Alabama
F
or many scientists, the phone call from a Nobel
Prize Awarding Institution informing them that
they have been awarded the Nobel Prize must
rank as one of the most important moments of their
lives. Martin Chalfie will remember the moment
somewhat differently. A recent change of ring tone
on his home phone meant he slept through the call
from Stockholm, thinking it was for someone else.
Chalfie laughs when recalling how he received the
happy news. “I woke up, and I realised that they
must have given the Prize in Chemistry, so I simply
said, ‘Okay, who’s the schnook that got the Prize this
time?’ And so I opened up my laptop, and I got to the
Nobel Prize site and I found out I was the schnook!”
C. elegans glowing with green fluorescent protein.
answered the phone and said something to the
effect of ‘Marty Chalfie, never heard of him’,” recalls
Chalfie. “And so Douglas Prasher got the idea that
I had dropped out of science. He didn’t tell me
because he didn’t think I was interested anymore.”
Chalfie says fortune eventually shone on him after
an opportune search of a medical database revealed
that Prasher had cloned GFP, and the pair
re-established contact. By that time, several research
groups were investigating whether GFP could glow
in other organisms. However, through no fault of
their own, the manner in which they were excising
Prasher’s GFP gene to create more of the gene
themselves was creating a protein
that didn’t glow. “That fragment had
extra little bits of sequence on either
end,” says Chalfie. “Apparently, it’s
those sequences that were poison.
The extra DNA interfered with the
protein production.” Chalfie, on
the other hand, had done things
differently. “We simply amplified exactly the coding
sequence from the clone, and didn’t have any of the
extra DNA.” When Chalfie tested whether his GFP
was working, it glowed.
“I work on this
transparent animal, this
is going to be terrific! I’ll
be able to see the cells
within the living animal”
Given the unlikely chain of events, and the manner
in which he discovered the news about his Nobel
Prize, Chalfie can be forgiven for wondering if he is
still sleeping. “I’ll try to wake up tomorrow and say
that it wasn’t a dream!”
This article is based on a telephone interview with Martin Chalfie following the announcement of the 2008 Nobel Prize in Chemistry.
To listen to the interview in full, visit http://nobelprize.org/nobel_prizes/chemistry/laureates/2008/chalfie-interview.html
chemistry 11
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2008 nobel Laureates
In his own words: Roger Tsien
L
A love of pretty colours can be said to have been
the driving force in Tsien’s research career.
“I have to say I myself do not find pipetting
colourless droplets of liquid from one plastic
tube to another awfully inspiring.” says Tsien.
“At least without having to worry about whether
the work would be successful in 5 or 10 or 20
years, I could get some direct aesthetic pleasure
out of the experiments as I went along.”
When asked to comment on the observation that
this Nobel Prize in Chemistry is being awarded
for work that is basically involved in cell
biology, Tsien notes that it’s an area that has
been categorised as being chemical biology,
biochemistry, or as Tsien sometimes calls it,
“We try to build molecules
to solve problems”
Roger Tsien’s range of fluorescent proteins have
brought some colour to laboratory work.
molecular engineering, “at least our approach
to it, because we try to build molecules to solve
problems.”
Does Tsien worry about these academic labels?
“I try not to,” he replies, but adds that it becomes
dangerous “when students let themselves get
pigeon-holed, or let their thought processes get
pigeon-holed, and they say ‘Oh, I could never do
that, that’s chemistry. I don’t know any chemistry’.”
It’s surprising how often biologists develop an
attitude about chemistry or chemists an attitude
about biology, says Tsien, which unfortunately
creates an “instinctual fear that, ‘Oh, that’s a subject
I can’t do, and nobody should expect me to know
how to do, and so I will just not pay any attention to
questions that lead me in that direction’.” If there is
one thing that Tsien has illustrated over the years, it’s
the importance of being illuminated by any direction
the subject that you are interested in takes you.
Tsien Lab, University of
California, San Diego
As an adult chemist, Tsien has been instrumental
in making the green fluorescent protein a more
effective beacon for visualising processes inside
cells. By understanding what made GFP glow and
by tweaking the structure he could create molecules
that emit light at slightly different wavelengths,
producing tags of different colours. From the tens of
thousands of papers that have been published using
the probes he has developed, Tsien finds it difficult
to single out any of the applications that he likes
the most. One of the “showiest applications”,
he says, is the trick of painting neurons in a whole
kaleidoscope of colours – known as the brainbow.
Tsien Lab, University of California,
San Diego
ike many Nobel Laureates, Roger Tsien says
his love of science began at an early age,
carrying out chemistry experiments at home,
accompanied with “a mixture of fear in my parents
and a little bit of encouragement”. By the relatively
early age of 9 or 10, he knew he wanted to be a
scientist. “I think I did go through the usual smallchild phase of imagining being a fireman and so on,
but yeah, I think being a scientist was more of a
possibility for me than probably for most kids.”
Scientists can now use a palette of different
coloured tags to visualise processes inside cells.
This article is based on a telephone interview with Roger Tsien following the announcement of the 2008 Nobel Prize in Chemistry.
To listen to the interview in full, visit http://nobelprize.org/nobel_prizes/chemistry/laureates/2008/tsien-interview.html
12 chemistry
Copyright © Nobel Web AB 2008. Nobelprize.org, Nobel Prize and the Nobel Prize medal design mark are registered trademarks of the Nobel Foundation.